Proximity- and Chelation-Induced S_NAr 1,4-Aromatic ortho-Substitution of ortho-Methoxyphenyl 2-Alkyl Ketones

Abstract

The direct displacement of an o-methoxy group in o-methoxyaryl ketones with aryl, alkyl, and alkenyl Grignard reagents to provide a series of o-substituted ketones is described. Application of this reaction to the synthesis of a C-methyl analogue of a cyclooxygenase inhibitor is shown. The scope and limitations are discussed.

Key words

aromatic substitution - biaryls - Grignard reaction in aryl ketones - steric hindrance - transition-metal-free reactions

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